Endothelial-to-Mesenchymal Transition in Bone Marrow and Spleen of Primary Myelofibrosis

Abstract

Primary myelofibrosis is characterized by the development of fibrosis in the bone marrow that contributes to ineffective hematopoiesis. Bone marrow fibrosis is the result of a complex and not yet fully understood interaction among megakaryocytes, myeloid cells, fibroblasts, and endothelial cells. Here, we report that >30% of the endothelial cells in the small vessels of the bone marrow and spleen of patients with primary myelofibrosis have a mesenchymal phenotype, which is suggestive of the process known as endothelial-to-mesenchymal transition (EndMT). EndMT can be reproduced in vitro by incubation of cultured endothelial progenitor cells or spleen-derived endothelial cells with inflammatory cytokines. Megakaryocytes appear to be implicated in this process, because EndMT mainly occurs in the microvessels close to these cells, and because megakaryocyte-derived supernatant fluid can reproduce the EndMT switch in vitro. Furthermore, EndMT is an early event in a JAK2-V617F knock-in mouse model of primary myelofibrosis. Overall, these data show for the first time that microvascular endothelial cells in the bone marrow and spleen of patients with primary myelofibrosis show functional and morphologic changes that are associated to the mesenchymal phenotype.

Megakaryocyte contribution to bone marrow fibrosis: many arrows in the quiver

“… 96 Further, Erba et al showed that release and activation of TGF-β1 by Mks and platelets, forced endothelial cells from the BM microvasculature of PMF patients, and mouse model of PMF, to acquire a mesenchymal phenotype through Endothelial Mesenchymal Transition (EndMT), during the development of fibrosis. 97 …”

Pathological findings that contribute to tissue stiffness in the spleen of liver cirrhosis patients

“…Recently, Erba et al . reported that endothelial‐to‐mesenchymal transition (EndoMT) produces αSMA expression of splenic sinus endothelial cells (SECs) and fibrosis in the spleen of patients with primary myelofibrosis . Endothelial cells contribute to neovascularization of the injury region and promote repair .…”

“…Endothelial‐to‐mesenchymal transition is a relatively common reaction of different types of endothelial cells. As its name implies, during EndoMT, endothelial cells show gene expression patterns similar to those of myofibroblasts, including gene expression of αSMA, fibroblast‐specific protein‐1, and collagen type I . Portal hypertension causes endothelial dysfunction in the splanchnic and systemic circulation .…”

Industrial Solvents: Underlying Potential Risks of Left-Sided Potal Hypertension Associated with Positive JAK2-V617F Gene

“…In reality, JAK2-V617F has been proved in connection with Myeloproliferative Neoplasams (MPNs) [9][10]. As we all know, MPNs are a group of hematopoietic stem cell disorders characterized by clonal proliferation of myeloid-lineage cells [11].…”